Article
Chemistry, Multidisciplinary
Alexander Kremsmair, Andreas Hess, Benjamin Heinz, Paul Knochel
Summary: Mixed TMP-bases are excellent reagents for the metalation of functionalized aromatics and heterocycles. By combining with Lewis acids, the metalation scope can be increased, and regioselectivity switches can be achieved. Highly reactive lithium bases are also compatible with various Lewis acids, and performing metalations in continuous flow using commercial setups allows for practical and convenient reaction conditions.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Sebastian Heindl, Margaux Riomet, Jan Matyasovsky, Miran Lemmerer, Nicolas Malzer, Nuno Maulide
Summary: A chemoselective and robust protocol for the gamma-oxidation of beta,gamma-unsaturated amides has been developed, showcasing the synthetic utility of the products obtained through radical cyclisation reactions and oxidation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Nabin Sarkar, Rajata Kumar Sahoo, Sharanappa Nembenna
Summary: In this study, a molecular aluminium dihydride complex was used as a catalyst for reducing a wide range of aryl and alkyl esters, showing good tolerance towards other functional groups. The catalytic application of aluminium dihydride in the C-O bond cleavage of alkyl and aryl epoxides was also investigated, resulting in branched Markovnikov ring-opening products.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Xiao-Lin Wang, Ji-Teng Chen, Sheng-Cai Zheng, Xiao-Ming Zhao
Summary: The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one, derived from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione, in iridium-catalyzed allylic enolization is achieved under mild conditions. The presence of a quaternary carbon and adjustment of reaction conditions enable high selectivities in terms of chemoselectivity, regioselectivity, and enantioselectivity. This method provides substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with excellent chemo-, regio-, and enantioselectivities. Additionally, the formation of chiral carbon-fluorine bonds is induced by an adjacent chiral carbon center.
Article
Chemistry, Applied
Yeong-Jiunn Jang, Guan-Yu Chen, Yun-Lian Jhan, Pei-Ting Lo, Wei-Yu Hsu, Ke Wang, Ya-Ting Hsu, Chia-Lin Lee, Yu-Liang Yang, Yang-Chang Wu
Summary: A one-pot synthesis of substituted isocoumarin, flavone, and isoquinolinedione derivatives has been developed using a switchable C-arylation/lactonization or SNAr reaction. This base-mediated protocol proceeds under transition-metal-free conditions and selectively affords various heteroarenes in good yields. The synthetic utility of this method is demonstrated in the synthesis of potential anti-HIV and anti-coronavirus derivatives and COX-2 inhibitors. Detailed experimental and computational studies provide a comprehensive understanding of the reaction mechanism.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Physical
Bing Zhang, Xueying Guo, Lei Tao, Ruolin Li, Zhenyang Lin, Wanxiang Zhao
Summary: The deoxygenative reduction of 1,3-diketones using a rhodium-catalyzed method exhibits high regioselectivity toward aliphatic carbonyl reduction, good functional group tolerance, and potential in the late-stage modification and synthesis of natural products and pharmaceutical skeletons. Preliminary mechanistic studies suggest a lower energy barrier for aliphatic C = O insertion, explaining the high regioselectivity observed in this reduction.
Article
Chemistry, Multidisciplinary
Alexander Kremsmair, Alisa S. Sunagatullina, Leonie J. Bole, Pasquale Mastropierro, Simon Grassl, Henrik R. Wilke, Edouard Godineau, Eva Hevia, Paul Knochel
Summary: A new method for selectively zincating challenging N-heterocyclic substrates has been reported using mixed Li/Zn bases. The method allows for mild regioselective reactions and provides insights into the composition and reactivity of the reaction mixtures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Yuse Kuriyama, Yusuke Sasano, Yoshihiko Hoshino, Shun-ichiro Uesugi, Aoto Yamaichi, Yoshiharu Iwabuchi
Summary: Highly regioselective intramolecular aminolysis of 3,4-epoxy amines has been achieved by chemoselective activation of epoxides in the presence of unprotected aliphatic amines in the same molecules using a La(OTf)(3) catalyst, resulting in excellent regioselectivity for anti-Baldwin 5-endo-tet cyclization and stereospecific formation of 3-hydroxy-2-alkylpyrrolidines in high yields. DFT calculations suggested that regioselectivity is attributed to distortion energies of epoxy amine substrates. This reaction was used in the enantioselective synthesis of an antispasmodic agent prifinium bromide.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Xuelun Duan, Nan Zheng, Ming Li, Xinhao Sun, Zhuye Lin, Pan Qiu, Wangze Song
Summary: Remote ether groups can be utilized as directing groups to achieve exclusive 1,5-regioselectivities and excellent chemoselectivities in the synthesis of fully substituted 5-ether-1,2,3-triazoles. Coordination of ether group with iridium catalyst enables control of regioselectivity through weak coordination effect. The chemoselective cycloaddition reaction occurs at the propargyl ether moiety of diyne, yielding unique fully substituted 4-alkynyl-triazole.
CHINESE CHEMICAL LETTERS
(2021)
Review
Chemistry, Multidisciplinary
Yang Ke, Wei Li, Wenfeng Liu, Wangqing Kong
Summary: Scaffold diversity is crucial for the success of compound libraries in biological screening. This review focuses on recent efforts in Ni-catalyzed divergent and selective synthesis, which generate structurally diverse molecular scaffolds using the same substrate and varying the ligand backbone under almost identical reaction conditions. The progress achieved encourages the design and development of new selective catalytic systems and reveals new modes of catalytic transformation for broader synthetic applications.
SCIENCE CHINA-CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Dimitrije Djukanovic, Maximilian A. Ganiek, Kohei Nishi, Konstantin Karaghiosoff, Kazushi Mashima, Paul Knochel
Summary: A new convenient method for the preparation of dicarbamoylzincs is reported in this study. The target compounds were obtained by reacting ZnCl2 and formamides or TMP2Zn with formamides. This method is compatible with sensitive functional groups such as esters, ketones, or nitro groups. The reaction of these dicarbamoylzincs with various functionalized allylic, benzylic, aryl, alkenyl compounds, acid chlorides, aldehydes, or enones resulted in the synthesis of polyfunctional amides in high yields. The C-13 NMR characterization of these new compounds is presented.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Tessa R. Young, Maria Alessandra Martini, Andrew W. Foster, Arthur Glasfeld, Deenah Osman, Richard J. Morton, Evelyne Deery, Martin J. Warren, Nigel J. Robinson
Summary: Researchers have developed a metalation-calculator to elucidate metal occupancies in cells, showing how competition and variable metal availability affect metal binding to three different proteins in vivo.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Juan Ye, Yang Wang
Summary: A comprehensive study on the mechanisms and origins of the chemoselectivity and regioselectivity of phosphine-catalyzed Rauhut-Currier reaction is performed by DFT. The computational results reveal that the cross R-C reaction is energetically favorable, with head-to-tail product being generated preferentially. The C-C bond formation process is identified as the determining step for regioselectivity and chemoselectivity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Applied
Nian Zheng, Wei-Yu Shi, Ya-Nan Ding, Xue-Yuan Liu, Yong-Min Liang
Summary: Controllable chemoselectivity and regioselectivity synthesis of 3-sulfinylated, 3-sulfenylated and 2-sulfonylated indoles via direct C-H functionalization are achieved under metal-free conditions. The synthesis of 3-arylsulfinylindoles in high yields from a sulfone substrate in water without additives is particularly noteworthy. The use of p-Toluenesulfonyl cyanide (TsCN) as a new sulfur reagent through the cleavage of S-C and S=O bonds is also demonstrated.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Neil R. R. Judge, Eva Hevia
Summary: By adding two molar equivalents of KOtBu to Zn(TMP)(2) (TMP=2,2,6,6-tetramethylpiperidide), the mild zinc bis-amide base is transformed into a powerful metalating agent capable of regioselective zincation of sensitive fluoroarenes. The intermediates formed during Zn-H exchange are structurally verified, showing the activation of TMP groups to generate higher order bis-aryl potassium zincates. This bimetallic KOtBu/Zn(TMP)(2) partnership exhibits the ability to zincate toluene and benzene at room temperature.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Organic
Baosheng Wei, Paul Knochel
Summary: Cross-couplings involving organozinc reagents can proceed well in the absence of transition-metal catalysts with reactive electrophiles. Highly diastereoselective and enantioselective cross-couplings can be readily performed with room-temperature configurationally stable alkylzinc species, producing diastereoselectively and enantiomerically enriched products. Highly regioselective magnesiations of functionalized arenes and heteroarenes undergo Negishi or Cu-catalyzed cross-couplings.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Alisa S. Sunagatullina, Ferdinand H. Lutter, Paul Knochel
Summary: In this study, various dialkylmagnesiums were synthesized by reacting primary or secondary alkyl iodides with sBu(2)Mg, and these reagents underwent diverse reactions with different compounds to yield stereodefined products. Mechanistic studies revealed that these reactions proceed via a radical pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Alexander Kremsmair, Andreas Hess, Benjamin Heinz, Paul Knochel
Summary: Mixed TMP-bases are excellent reagents for the metalation of functionalized aromatics and heterocycles. By combining with Lewis acids, the metalation scope can be increased, and regioselectivity switches can be achieved. Highly reactive lithium bases are also compatible with various Lewis acids, and performing metalations in continuous flow using commercial setups allows for practical and convenient reaction conditions.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
A. Hess, H. C. Guelen, N. Alandini, A. Mourati, Y. C. Guersoy, P. Knochel
Summary: This study presents a novel method for the selective ortho, ortho'-functionalization of readily available aryl oxazolines using sBu(2)Mg in toluene followed by trapping reactions with electrophiles. The conversions of these nitriles to valuable heterocycles are reported, and a tentative mechanism is proposed for the reactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Benjamin Heinz, Dimitrije Djukanovic, Fiona Siemens, Mohamed Idriess, Benjamin Martin, Paul Knochel
Summary: The treatment of 3-halopyridines with certain R-substituents in specific positions using specific reagents under specific conditions provided regioselectively synthesized a series of aminated pyridine compounds with high yields. These substitution reactions may proceed via pyridyne intermediates.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Multidisciplinary
Dimitrije Djukanovic, Maximilian A. Ganiek, Kohei Nishi, Konstantin Karaghiosoff, Kazushi Mashima, Paul Knochel
Summary: A new convenient method for the preparation of dicarbamoylzincs is reported in this study. The target compounds were obtained by reacting ZnCl2 and formamides or TMP2Zn with formamides. This method is compatible with sensitive functional groups such as esters, ketones, or nitro groups. The reaction of these dicarbamoylzincs with various functionalized allylic, benzylic, aryl, alkenyl compounds, acid chlorides, aldehydes, or enones resulted in the synthesis of polyfunctional amides in high yields. The C-13 NMR characterization of these new compounds is presented.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Andreas Hess, Nurtalya Alandini, Yusuf C. Guersoy, Paul Knochel
Summary: A new and storable magnesium amide was prepared and found to be suitable for the non-cryogenic magnesiation of fluoro-substituted arenes and heteroarenes. Further reactions produced a range of polyfunctional fluoro-substituted unsaturated building blocks.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Johannes H. Harenberg, Rajasekar Reddy Annapureddy, Konstantin Karaghiosoff, Paul Knochel
Summary: This study reports a lateral sodiation reaction for alkyl(hetero)arenes using a hexane-soluble sodium compound generated on demand, in the presence of TMEDA. The reaction can be conducted under batch and continuous flow conditions. The resulting benzylic sodium species can react with various electrophiles. This method has great potential for synthetic applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Saroj Kumar Rout, Agonist Kastrati, Harish Jangra, Kuno Schwaerzer, Alisa S. Sunagatullina, Maximilien Garny, Fabio Lima, Cara E. Brocklehurst, Konstantin Karaghiosoff, Hendrik Zipse, Paul Knochel
Summary: DFT calculations can predict the reactivity of uncommon N-heterocyclic scaffolds and facilitate their functionalization. Experimental results show that specific catalysts and reagents can achieve the regioselective derivatization of these compounds.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Alexander Kremsmair, Alisa S. Sunagatullina, Leonie J. Bole, Pasquale Mastropierro, Simon Grassl, Henrik R. Wilke, Edouard Godineau, Eva Hevia, Paul Knochel
Summary: A new method for selectively zincating challenging N-heterocyclic substrates has been reported using mixed Li/Zn bases. The method allows for mild regioselective reactions and provides insights into the composition and reactivity of the reaction mixtures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Alexander Kremsmair, Henrik R. R. Wilke, Johannes H. H. Harenberg, Benjamin R. G. Bissinger, Matthias M. M. Simon, Nurtalya Alandini, Paul Knochel
Summary: This study reports a practical in situ quench procedure for the generation of chiral secondary alkyl lithiums from secondary alkyl iodides. The reaction can be carried out in the presence of various electrophiles, resulting in the preparation of a wide range of optically enriched organic compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Alisa S. Sunagatullina, Andreas Hess, Alexander Kremsmair, Yifan Li, Yi-Hung Chen, Paul Knochel
Summary: We present a novel electrophilic amination method for primary, secondary, and tertiary alkyl, benzylic, and allylic zinc and magnesium organometallics using O-2,4,6-trimethylbenzoyl hydroxylamines (O-TBHAs) with yields ranging from 52-99%. These O-TBHAs exhibit excellent long-term stability and can be conveniently synthesized from various highly functionalized secondary amines through a three-step procedure. The amination reactions demonstrate remarkable chemoselectivity without the need for transition-metal catalysts, and are typically completed within 1-3 hours at 25 degrees Celsius. Furthermore, this electrophilic amination process enables the synthesis of enantioenriched tertiary amines (up to 88% ee) using optically enriched secondary alkylmagnesium reagents of the type s-AlkylMgCH(2)SiMe(3).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Clemence Hamze, Julie Brossier, Konstantin Karaghiosoff, Edouard Godineau, Paul Knochel
Summary: A regioselective tri- and tetra-functionalization of the pyridazine scaffold was achieved using two readily available building blocks, resulting in the synthesis of a range of pyridazine derivatives.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Agonist Kastrati, Alexander Kremsmair, Alisa S. Sunagatullina, Vasilii Korotenko, Yusuf C. Guersoy, Saroj K. Rout, Fabio Lima, Cara E. Brocklehurst, Konstantin Karaghiosoff, Hendrik Zipse, Paul Knochel
Summary: Straightforward calculations have led to the development of a set of organometallic reactions for the regioselective functionalization of the underexplored fused N-heterocycle imidazo[1,2-a]pyrazine. These reactions provide a way to access polyfunctionalized imidazopyrazine heterocycles.
Article
Chemistry, Multidisciplinary
Andreas Hess, Nurtalya Alandini, Hasret C. Guelen, Jan P. Prohaska, Paul Knochel
Summary: We report the preparation of a new hydrocarbon-soluble magnesium amide TMP2Mg (TMP = 2,2,6,6-tetramethylpiperidyl). This base showed excellent properties for the regioselective magnesiation of various arenes and heteroarenes bearing ethyl esters and carbamates under very mild reaction conditions. Subsequent trapping with aryl iodides (Negishi cross-coupling) gave access to a range of highly functionalized valuable building blocks.
CHEMICAL COMMUNICATIONS
(2022)